|Haley, Rani - UAMS/ACNC|
|Hidestrand, Mats - UAMS/ACNC|
|Shankar, Kartik - UAMS/ACNC|
|Lumpkin, Charles - UAMS/ACNC|
|Yarberry, Brandi - UAMS/ACNC|
|Badger, Thomas - UAMS/ACNC|
|Ronis, Martin - UAMS/ACNC|
Submitted to: Toxicologist
Publication Type: Abstract Only
Publication Acceptance Date: October 3, 2004
Publication Date: March 15, 2005
Citation: Haley, R., Hidestrand, M., Shankar, K., Lumpkin, C.K., Yarberry, B., Badger, T.M., Ronis, M.J. Estradiol protects against ethanol-induced bone loss in female rats by preventing osteoclast activation. The Toxicologist. 84(S-1):354. Interpretive Summary: Maintaining good density is essential to preventing osteoporosis. One nature physiological process in which bone density decreases in women occurs during pregnancy and lactation, when the are tremendous needs for minerals for fetal bone development and growth. There are is a significant number of American women who obtain a significant percentage of the daily calories through alcohol. Alcohol has been known to decrease bone density and we studied the effects of estrogen and progesterone on the ability of alcohol to reduce bone density. We found that estrogen prevented bone density decreases due to alcohol and the mechanism appears to be by preventing the bone cell type responsible for breakdown bone. Future studies will determine how this information can be applied to women with low bone density.
Technical Abstract: We have previously shown that pregnancy reduces the bone loss observed with alcohol consumption in female rats. We tested the idea that this protection might be due to increased circulating sex steroids. In the current study, 225 g female Sprague-Dawley rats (N = 6/group) were infused liquid diets directly into the stomach with or without alcohol replacing carbohydrate calories at a dose of 13 g/kg/d for 21 d. Additional control and EtOH groups were supplemented with the female sex srteroids 17 beta-estradiol (E2, 20 ug/kg/d via osmotic minipump) or with E2 + progesterone (P, 75 mg/kg/d s.c. in corn oil vehicle). At the end of the study E2 supplementation increased plasma E2 values from 3 + 1 to 66 + 12 pg/ml (p < 0.05) and P supplementation increased P values from 12 + 6 to 225 + 31 ng/ml (p < 0.05) in EtOH-treated rats, values similar to or higher than those observed in pregnancy. While E2 supplementation had no effect on tibial bone density in control rats, E2 prevented ethanol-induced bone loss. Bone density was greater in the E2 + EtOH than in the EtOH group (p < 0.05) as measured by peripheral quantitative computerized tomography both in the live animal and in isolated tibial bone. In addition, measurement of plasma collagen type I fragments (RatLapsTM) as a marker of osteoclast-mediated bone loss demonstrated increases with EtOH and suppression in the E2 + EtOH group (p < 0.05). In contrast, both EtOH and E2 reduced plasma osteocalcin, a bone formation marker in an additive fashion (p < 0.05). The E+P group had no significant effects compared to supplementation with E2 alone. These data suggest E2 protects against ethanol-induced bone loss by preventing ethanol-associated osteoclast activation.